Pharmacologic challenges of vulnerable individuals constitute an important study paradigm for elucidating possible mechanisms for the pathophysiology of alcoholism. This paradigm has yielded information on possible differences in metabolism and effects of alcohol among subjects who are assumed to be at high and low risk for the development of problems with alcohol use by virtue of having a family history of alcoholism. These high risk studies, however, have generally not considered the role of diagnostic comorbidity in the familial transmission of alcoholism. Recent work in this area by members of our research group has demonstrated co-segration of alcoholism and anxiety disorders in families. This suggests that there may be a subtype of alcoholism associated with anxiety disorders. The present study is designed to examine possible mechanisms for the association between alcoholism and anxiety disorders. The hypothesis to be examined is that individuals with a family history of anxiety and alcoholism experience an enhanced ability to experience a reduction of cardiovascular and cognitive responses to stress following alcohol consumption. To test this hypothesis, groups of non-alcoholic men and women will be selected on the basis of parental psychiatric history as follows: 1) alcoholism only; 2) alcoholism and anxiety; 3) anxiety only; 4) neither alcoholism or anxiety (controls). Direct diagnostic assessments of the subject's biological parents will be made in order to minimize the possible risk of bias associated with family history information. These groups will be compared on cardiovascular, electrodermal and self-reported anxiety in response to a speech stressor under conditions of placebo and alcohol. Other putative markers of risk factors for the development of alcoholism will also be assessed and integrated with these data. The study results will provide information regarding the specificity and generalizability of these parameters with respect to alcoholism and anxiety disorders. Ultimately, the findings could have important implications for the identification and prevention of alcoholism in vulnerable individuals.